Lp(a) plasma concentrations are highly heritable[9][10] and mainly controlled by the LPA gene[11] located on chromosome 6q25.3–q26.
Specifically, the larger the isoform, the more apo(a) precursor protein accumulates intracellularly in the endoplasmic reticulum.
Lp(a) is not fully synthesised until the precursor protein is released from the cell, so the slower rate of production for the larger isoforms limits the plasma concentration.
[18][19] The general inverse correlation between apo(a) isoform size and Lp(a) plasma concentration is observed in all populations.
[citation needed] In addition to size effects, mutations in the LPA promoter may lead to a decreased apo(a) production.
[21] Lp(a) is assembled at the hepatocyte cell membrane surface, which is similar to typical LDL particles.
[30] Moreover, Lp(a) carries atherosclerosis-causing cholesterol and binds atherogenic pro-inflammatory oxidised phospholipids as a preferential carrier of oxidised phospholipids in human plasma,[31] which attracts inflammatory cells to vessel walls and leads to smooth muscle cell proliferation.
[32][33][34] Moreover, Lp(a) also is hypothesised to be involved in wound healing and tissue repair by interacting with components of the vascular wall and extracellular matrix.
[citation needed] Since apo(a)/Lp(a) appeared rather recently in mammalian evolution — only old world monkeys and humans have been shown to harbour Lp(a) — its function might not be vital, but just evolutionarily advantageous under certain environmental conditions, e.g. in case of exposure to certain infectious diseases.
[20] Another possibility, suggested by Linus Pauling, is that Lp(a) is a primate adaptation to L-gulonolactone oxidase (GULO) deficiency, found only in certain lines of mammals.
Results using statin medications have been mixed in most trials, although a meta-analysis published in 2012 suggests that atorvastatin may be of benefit.
[44][45] High Lp(a) correlates with early atherosclerosis independently of other cardiac risk factors, including LDL.
Lp(a) accumulates in the vessel wall and inhibits the binding of PLG to the cell surface, reducing plasmin generation, which increases clotting.
[47] Researchers in studies in 1995 and 1998 concluded that regular consumption of moderate amounts of alcohol led to a significant decline in plasma levels of Lp(a).
[3] Animal studies have shown that Lp(a) may directly contribute to atherosclerotic damage by increasing plaque size, inflammation, instability, and smooth muscle cell growth.
[4] The European Atherosclerosis Society currently recommends that patients with a moderate or high risk of cardiovascular disease should have their Lp(a) levels checked.
In addition, the patient's other cardiovascular risk factors (including LDL levels) should be managed optimally.
[62] The current simplest treatment for elevated Lp(a) is to take 1–3 grams of niacin daily, typically in an extended-release form.
[63] However more recent research suggests that the inflammatory effects of the breakdown products of excess niacin lead to an increase in risk of major adverse cardiovascular event.
[67][71] The American Academy of Pediatrics now recommends that all children between the ages of nine and eleven years old be screened for hyperlipidemia.